From the beginning, our strategy has been to understand the overall picture regarding ethics, sustainability, safety, and security in our project. Thereafter, we have tried to find all the specific issues with our project and how we can solve and integrate them into our work.
We early on identified and analysed the different stakeholders, and opened up a discussion regarding the many aspects and opinions that could affect our project. We aim to create a therapeutic product, which is why we have targeted regulatory consultants, business advisors, doctors, patients, ethics professors and health economics professors. Along the way, we were able to identify and integrate different parts such as safety, regulations and product design. However, we also wanted to create valuable content that we believe can positively can influence, inspire, and help current and future iGEM teams, while improving Human Practices.
We faced one of our biggest challenges early on in the project. We realized that if our product PROlung was to be released on the market, it would need to be safe and biocontained, for both for humans and for the environment.
These requirements have not been only established in order to obtain approval from the regulatory agencies, from our interviews we also learned that they were also very important from the doctor’s point of view, from their Hippocratic Oath they would never prescribe anything that could cause any harm, or could be unsafe for the patients.
Not only regulators and doctors raised their concern about this topic, during the Nordic iGEM Conference (NiC), we received the same feedback from an iGEM judge, that we would really need to consider all the safety issues a product like this could raise.
However, the first person raising this concern, and one of our most influential advisors for this topic is Giulio Bernardinelli, a member of iGEM Trieste 2011 and an advisor for iGEM Trieste 2012. He emphasized the importance of having a controllable switch and informed us of the issue regarding leaky toxin expression. His advice was to add an antitoxin to the switch used by the iGEM Trieste 2012 team and described by Choi et al. 2005, which uses a regulatory protein repressed by cumate. This second layer of protection would make the system safer and more tightly contained.
To solve this challenge we integrated a killswitch into our research as biocontainment measurement in our project.
As part of our project development, we researched the different regulations and directives that could be applied to our project, as a Recombinant Live Biotherapeutic Product (LBP), and despite our best efforts, we were surprised over the lack of information covering this topic. This made us realise that we would not be able to gather and map all the regulations related to our project on our own.
For this reason, we decided to get in contact with Erik Forsse, a senior adviser (specialist) at the Director’s Office at Karolinska Institutet, who works with investigations, analyses and the processing of in-coming public consultations. He explained that the current regulations for a project like ours does not exist, and inspired us to create a policy of our own.
Even with the support and knowledge that Erik had provided us, we understood that we needed to contact someone working with more in-depth knowledge about regulations. We contacted Katarina Mercer, Senior Advisor for Clinical Development & Regulatory Affairs at Scandinavian Development Services. She, once again, confirmed that there are no available regulations for our project. Katarina supported us in how we could develop our own policy by guiding us through similar cases and by providing us an insight in product development and what strategies we could use.
Additionally, we reached out to the Medical Products Agency (Swedish: Läkemedelsverket), the government agency in Sweden responsible for regulation and surveillance of the development, manufacturing and sales of medicinal drugs, medical devices and cosmetics. We talked to Åsa Kumlin Howell, international coordinator at the medical products agency, and she stated:
“This has been shown to be a hard question to answer, and after some research I haven't been able to find any legislation that regulates live biotherapeutic bacteria”
From these meetings we were able to determine our strategy for the policy we were aiming to create. The first part of the policy is an introduction to all current regulations regarding GMOs, live biotherapeutic product (LBP) and drug delivery systems as a first step to understanding how all these parts are perceived to-date. Further on, all the background information was analysed and a solution is proposed that assures the safety in the usage of LBP’s. The developed solution proposes an evaluation of Human Safety, Environmental Safety and risk assessment before any product with these characteristics can be approved for human use. Additionally, several final considerations on how clinical studies should be performed are also explained.
Together with the advices from Katarina, Åsa and Erik, we also incorporated the society's views on GMOs into our policy. For this reason, we thought it would be a good idea to host a GMO debate, where we would bring experts with different knowledge and opinions about the use of GMOs and initiate a discussion where the public could actively be engaged and build on an opinion on the subject. This event was held in collaboration with Uppsala University's iGEM team. The result of the panel discussion exceeded our expectations and was implemented into our policy.
However, we wanted to take the next step in the successful implementation of the policy we had been working on. Because of this, we handed the policy over to the Medical Products Agency, since they are the head governmental agency handling, regulating and in the end accepting new medicinal drugs in Sweden. Our goal is that in the future they use the policy we developed for the evaluation of future applications.
From the beginning of our project, we had the goal of always keeping the final customer in the center of the development of our idea. Because of this, we decided to conduct patient surveys, in order to understand their worries and needs, and how they experience life with these diseases. From these surveys we received significant information that helped us shape different parts of our project. Additionally, we interviewed six healthcare professionals such as doctors, nurses and physiotherapists about the need of a new medication and how it would be designed.
From the patient surveys we obtained that the preferred way of administrating our treatment would be to inhale it into the lungs. From the doctor interviews and research on the field, we were able to narrow it down to a nebulizer for the inhalation of the product over a longer period of time. Therefore we draw the conclusion that a type of inhalation device, such a nebulizer, would be the best device to use when treating these diseases.
This decision was further supported by our own literature research, as nebulizers would be able to be more efficient than any other device while having the lowest side effects associated to its use.
When we started our Human Practices, it was hard for us to understand exactly what human practices entangled and what was required for a team’s human practices to be successful. We had to spend a lot of time just reading about the topic to know where and how to start.
During NiC, informational presentations were held, in these presentations human practices were emphasized and displayed as something many teams forget about, put too little energy and/on or starts too late with. From these presentations, we had the idea to make a clear, easily understood handbook for all new teams to consider in the beginning of their human practices. We also skyped with the iGEM team from Lund (a new iGEM team!) and introduced the idea of a HP manual.They confirmed the need for such a handbook by saying “That is a great idea and it would've helped us a lot in the beginning if we had such a manual!”.
We decided to base the handbook on the work of previous successful Human Practices teams. We sent out questionnaires and received answers from Stockholm 2016, OLS Canmore 2016, Imperial 2016, Groningen 2016, Bielefeld 2015, William and Mary 2015, UofC Calgary 2016, Cornell NY 2016, Paris Bettencourt 2016.
From these teams, we received very positive feedback about our idea:
Luis Suarez from Groningen “I think it is a great idea of you to start such a manual! Starting HP can be confusing and challenging.”
Rachelle Varga from Calgary “What a great idea! I’d be happy to answer your questions about the 2016 UofC_Calgary iGEM team”
Allison Bricknell George from Paris Bettencourt “It´s a good idea, please share the result when you're done with this!”
Thanks to these teams, we were able to complete a great handbook for all new iGEM teams, so everyone can succeed in their human practices!